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Biomedical subjects

R Buhl

Publications and source records attributed to R Buhl.

At least 127 records · Page 7Linked to original sources
PubMed1995

The effects of prostacyclin on gastric intramucosal pH in patients with septic shock.

OBJECTIVE: To investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi). DESIGN: Interventional clinical study. SETTING: Surgical ICU in a university hospital. PATIENTS: 16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure. INTERVENTIONS: All patients received PGI2 (10 ng/kg x min) after no further increase in oxygen delivery could be obtained by volume expansion, red cell transfusion and dobutamine infusion. The results were compared with those before and after conventional resuscitation. The patients received continuous PGI2 infusion for 33-32 days. MEASUREMENTS AND RESULTS: O2 uptake was measured directly in the respiratory gases, pHi was determined by tonometry. Baseline O2 delivery, O2 uptake and pHi were 466 +/- 122 ml/min.m2, 158 +/- 38 ml/min.m2, and 7.29 +/- 0.09, respectively. While O2 uptake remained unchanged, infusing PGI2 increased O2 delivery (from 610 +/- 140 to 682 +/- 155 ml/min.m2, p < 0.01) and pHi (from 7.32 +/- 0.09 to 7.38 +/- 0.08, p < 0.001) beyond the values obtained by conventional resuscitation. While 9 of 11 patients with final pHi > 7.35 survived, all patients with final pHi < 7.35 died (p < 0.01). CONCLUSIONS: Infusing PGI2 in patients with septic shock increases pHi probably by enhancing blood flow to the splanchnic bed and thereby improves splanchnic oxygenation even when conventional resuscitation goals have been achieved.

Adult↗
PubMed1995

Surgical treatment of septic deep venous thrombosis.

BACKGROUND: Septic deep venous thrombosis (SDVT) is an uncommon but occasionally lethal disease caused by systemic complications. In most cases reported in the literature SDVT is caused by intravenous drug abuse or transvenous catheter lines. Conservative management with antibiotic drugs and systemic anticoagulation is usually successful, and the surgical approach is regarded as not indicated or unnecessary. Occasionally, however, conservative management fails, thrombosis progresses, and septic embolism develops. METHODS: In a 7-year period five patients (three male and two female; mean age, 21.2 years), three with severe systemic complications of SDVT (femoropopliteal, 1; iliofemoral, 1; iliofemoral+vena cava, 3), were treated by venous thrombectomy in addition to intravenous antibiotic administration. Simultaneous transabdominal caval thrombectomy was performed twice. RESULTS: Two patients suffered from respiratory failure caused by previous septic embolization. One patient had experienced multiorgan failure before thrombectomy was performed. Intensive care was necessary for all patients (mean, 28 days). All patients survived. CONCLUSIONS: In complicated cases of SDVT without improvement or even impairment after conservative management, venous thrombectomy is a lifesaving treatment.

Adolescent↗
PubMed1995

Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals.

Idiopathic pulmonary fibrosis (IPF) is characterized by a huge alveolar oxidant burden and a deficiency of glutathione, a major antioxidant, in the pulmonary epithelial lining fluid (ELF). Therefore, a rational therapeutic strategy is to increase lung glutathione to augment the pulmonary antioxidant protective screen. To evaluate this concept, different doses of N-acetylcysteine (NAC), a glutathione precursor, were administered intravenously to eight patients with pulmonary fibrosis and six control subjects. In patients, bronchoalveolar lavage fluid (BALF) total glutathione increased significantly from 0.99 +/- 0.25 microM to 1.79 +/- 0.37 microM within 3 h following 1.8 g NAC, whereas 4.8 g NAC had no additional effect (1.47 +/- 0.34 microM). In the control subjects, NAC did not significantly alter BALF total glutathione (baseline: 0.79 +/- 0.17 microM, 600 mg NAC: 0.92 +/- 0.33 microM, 1.8 g NAC: 1.39 +/- 0.41 microM, 4.8 g NAC: 1.33 +/- 0.46 microM). The same was true in ELF, 1.8 g NAC significantly raised ELF total glutathione in patients from 186 +/- 47 microM to near normal levels (373 +/- 103 microM), with no further increase following 4.8 g NAC (293 +/- 62 microM). In the control subjects, ELF total glutathione remained unchanged independent of the NAC dose (baseline: 342 +/- 91 microM, 600 mg NAC: 385 +/- 135 microM, 1.8 g NAC: 633 +/- 220 microM, 4.8 g NAC: 646 +/- 263 microM). The increases in total glutathione were almost entirely due to increased levels of reduced glutathione, the form functional as an antioxidant. No adverse effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1995

[Immunopathogenesis of extrinsic allergic alveolitis].

Inhalation of a variety of organic dusts may cause the onset of hypersensitivity pneumonitis (HP) finally leading to irreversible pulmonary fibrosis in some individuals. So far, the pathogenesis of HP remains partially unclear. Besides patient-related factors this is probably attributable to the complex composition of the causative dusts: in addition to specific antigens that may induce type III and type IV reactions they contain a variety of additional components like particles and toxins with the ability to promote several antigen-independent reactions. During an acute episode of HP a marked alveolitis dominated by polymorphonuclear cells develops. As we showed these polymorphonuclear cells are in an activated state and may therefore cause pronounced damage in the lung interstitium. Based on these and other findings we believe that polymorphonuclear cells are of predominant importance for the pathogenesis of HP.

Acute Disease↗
PubMed1995

[Pathogenesis of idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis or lone cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown origin carrying an unfavorable prognosis. A yet unidentified hazard triggers a chronic inflammatory infiltration of the lung parenchyma characterized by an accumulation of alveolar macrophages, neutrophil and eosinophil granulocytes, and lymphocytes. Cytokines released by the activated cells modulate the inflammatory events. Oxidants and proteases, mainly released by alveolar macrophages and neutrophil granulocytes, mediate the injury to the lung parenchyma, leading to loss of alveolar-capillary units. The ensuing repair process, mesenchymal cell proliferation and up-regulation of synthesis of collagen fibers and other components of connective tissue matrix, replaces lung parenchyma by fibrotic tissue, leading to irreversible pulmonary dysfunction.

Cytokines↗
PubMed1994

Imbalance between oxidants and antioxidants in the lungs of HIV-seropositive individuals.

Following the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system. Compared to cells from normal individuals, AM of asymptomatic HIV-seropositive (HIV+) individuals (CDC-stage II) spontaneously released significantly more superoxide anion (O2-.) (P < 0.002). The O2-. release by AM of HIV-infected individuals was comparable to the spontaneous O2-.-release by AM of cigarette smokers (P > 0.6), a condition often associated with chronic damage of respiratory tissues. The destructive effects of oxidants are normally suppressed by antioxidant defense systems. Evaluation of the concentrations of glutathione, a major component of the pulmonary antioxidant protective screen, demonstrated that the HIV+ state is also characterized by a significant glutathione deficiency in lung epithelial lining fluid (P < 0.001) and in venous plasma (P < 0.001). This suggests that the alveolar structures of HIV+ individuals are continuously exposed to increased amounts of toxic oxygen radicals without adequate protection, i.e. the reactive oxygen metabolites may cause sufficient tissue damage culminating in interstitial lung disease. Further, since many immune functions are susceptible to injury by extracellular oxidants, the consequences of an unsuppressed oxidant burden in the lung may amplify the extent of local immunocompromise. In addition, since glutathione plays an important role in modulating lymphocyte activation and effector functions independent of its antioxidant activity, the systemic glutathione deficiency may contribute to the progressive global immune dysfunction that characterizes HIV infection.

Adult↗
PubMed1994

Do barbiturates impair zymosan-induced granulocyte function?

PURPOSE: The dose-response relationship of commercially available preparations of methohexital, pentobarbital, phenobarbital, and thiopental and their respective drug-free solutions on granulocyte function was investigated to evaluate whether suppression of neutrophil chemiluminescence is mediated by the barbiturates themselves or by their drug-free solutions. Furthermore, it was assessed whether suppression of chemiluminescence is due to an interaction mainly with neutrophils or to free radical scavenging. METHODS: The dose-response effects of the four barbiturates on granulocyte function were tested by zymosan-induced neutrophil chemiluminescence and, in addition, in a cell-free chemiluminescence system. RESULTS: Methohexital and pentobarbital did not influence zymosan-induced neutrophil chemiluminescence, whereas phenobarbital and thiopental decreased neutrophil chemiluminescence in a dose-dependent fashion. Nonphysiological osmolality (531 mosmol/kg) caused this impaired neutrophil chemiluminescence at the greatest concentration of phenobarbital. Thiopental solely suppressed neutrophil chemiluminescence drug specifically. Because thiopental also reduced chemiluminescence generated in a cell-free system, free radical scavenging might contribute to the impaired neutrophil chemiluminescence observed with thiopental. CONCLUSIONS: With the exception of thiopental, barbiturates do not impair oxygen radical production during phagocytosis of neutrophils.

Cell-Free System↗
PubMed1994

Unspecific bronchial reactivity to carbachol in healthy subjects--effect of age and smoking habits.

Chronic inflammatory processes of the airways induced by long-time cigarette consumption are a crucial factor in the pathogenesis of chronic obstructive pulmonary disease. In contrast, the role of cigarette smoking in the pathogenesis of bronchial hyperreactivity (BHR) is still unclear. The aim of this study was to assess the effect of chronic cigarette consumption on pulmonary function tests and BHR in healthy subjects. 63 healthy smokers and 63 lifetime nonsmokers matched for sex, age, height and weight were evaluated. Pulmonary function was determined by body plethysmography and spirometry. Bronchial provocation was performed by inhalation of increasing doses of carbachol (up to 25 g/l) in isotonic NaCl solution. Pulmonary function tests were within normal limits in all subjects. Nevertheless, midexpiratory flow at 25% of forced vital capacity was significantly smaller, and functional residual capacity was significantly greater in middle-aged smokers (age: 40-60 years) compared to middle-aged nonsmokers (p < 0.05, both comparisons). In young smokers and nonsmokers (age: 20-30 years) pulmonary function tests were not different (p > 0.28, all comparisons). Importantly, the carbachol concentration that provoked a 50% rise in specific airway resistance (PD50sRaw) was similar in smokers and nonsmokers of both age groups (p > 0.05, both comparisons) and did not correlate with the age of the subjects (p > 0.2). No correlations between baseline values of pulmonary function tests and PD50sRaw were observed (p > 0.34, all comparisons). The observations confirm that the distribution profile of BHR is unimodal and apparently not affected by age and smoking habits.

Adult↗
PubMed1994

The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by an increased oxidant burden and by a deficiency of glutathione, a major antioxidant, in the lung epithelial lining fluid (ELF). Therefore, a rational therapeutic approach is to reverse the imbalance between oxidants and antioxidants in the lung by enhancing the antioxidant screen. With this background, the aim of our study was to evaluate oral N-acetylcysteine (NAC) as a strategy to augment lung glutathione levels in patients with IPF. Concentrations of total glutathione in bronchoalveolar lavage fluid (BALF) were quantified spectrophotometrically, before and following oral therapy with 3 x 600 mg NAC per day for 5 days, in 17 nonsmoking patients with biopsy-proven IPF. The volume of ELF recovered by BAL was determined using the urea method. Pretherapy, total glutathione levels in ELF in IPF patients were significantly less than normal (187 +/- 36 vs 368 +/- 60 microM), in contrast to levels in BALF (0.99 +/- 0.12 vs 1.18 +/- 0.19 microM). Following therapy with oral NAC, glutathione levels in BALF were 1.54 +/- 0.24 microM (a significant increase compared to pretherapy), whereas the increase in ELF levels (319 +/- 92 microM) did not reach significance. The therapy was well-tolerated, and all routine clinical and bronchoscopic parameters remained unchanged. It is thus feasible and safe to augment deficient lung glutathione levels in patients with IPF; thereby, potentially augmenting pulmonary antioxidant protection.

Acetylcysteine↗
PubMed1994

[Therapy of lung diseases with antiproteases].

Neutrophil elastase (NE) is the most important protease of the human lung; if not inhibited NE is able to attack nearly all structural proteins and components of the immune system of the lung. In the normal human lung this is prevented by an excess of protease inhibitors. Based on quantitative and kinetic analyses alpha 1-antitrypsin (AAT) is the most important protease inhibitor of the human lung followed by the Secretory Leukoprotease Inhibitor (SLPI). As protease inhibitors may be inactivated by proteases and reactive oxygen metabolites released from polymorphonuclear cells, it is not surprising that some lung diseases--in particular lung emphysema caused by AAT deficiency, cystic fibrosis and ARDS--are characterized by an imbalance between proteases and protease inhibitors. Because uninhibited NE seems to play an important role in the pathogenesis of these diseases, it is obvious to use protease inhibitors as drugs. Up to now in most studies in men AAT purified from human plasma has been used: worldwide a substantial number of patients with lung emphysema caused by AAT deficiency is treated continuously; in addition AAT was aerosolized to patients with cystic fibrosis in a short term study with results suggesting that this therapy is efficient at least on a biochemical basis. We performed in vitro and in vivo animal studies with the recombinant form of SLPI (rSLPI). In these experiments we found that aerosolized rSLPI a) is not altered in its form or function in the first 13 h following aerosol; b) has a half-tie of 12 h in the lung; c) reaches the interstitium of the lung in intact form.(ABSTRACT TRUNCATED AT 250 WORDS)

Endopeptidases↗
PubMed1994

Do barbiturates and their solutions suppress FMLP-induced neutrophil chemiluminescence?

The dose-response relationship of four commercially available barbiturates (methohexitone, pentobarbitone, phenobarbitone and thiopentone) and of their drug-free solutions on the production of oxygen radicals by neutrophils were tested by N-formylmethionyl-leucyl-phenylalanine (FMLP)-induced granulocyte chemiluminescence and in a cell-free chemiluminescence system. Methohexitone had no effect on neutrophil chemiluminescence. Pentobarbitone, phenobarbitone and thiopentone dose-dependently decreased FMLP-induced chemiluminescence and cell-free chemiluminescence. Suppression of neutrophil chemiluminescence by pentobarbitone and phenobarbitone was due to effects of the drug-free solutions and an osmolality greater than 360 mosmol kg-1. Only thiopentone suppressed granulocyte chemiluminescence drug-specifically. The physicochemical properties of commercially available barbiturate preparations and their solutions, as well as free radical scavenging capacity, have to be considered if these preparations are used to evaluate drug-specific effects on the production of oxygen radicals by neutrophils.

Barbiturates↗
PubMed1994

In vivo assessment of pulmonary oxidant damage: the role of bronchoalveolar lavage.

Oxidants can cause injury and cell death by modifying and/or disturbing the structure and function of any cellular or non-cellular component. There is overwhelming evidence that a variety of lung disorders are mediated, at least in part, by oxidants causing tissue damage, especially since its location, anatomy, and function makes the lung a primary target for oxidant injury. Bronchoalveolar lavage (BAL) is an excellent tool to evaluate these mechanisms in vivo. BAL allows the repetitive sampling of the cellular and non-cellular components of the fluid lining the epithelium of the lower respiratory tract with minimal risk and discomfort for the patient. The analysis of cell numbers, differential cell counts, cellular functions, and concentrations and functional properties of non-cellular components of BAL fluid continuously improves our understanding of the pathogenesis of lung diseases and of the pathogenetic role of oxidants and antioxidants in particular, by "looking into the living lungs." Further, the ready access of the respiratory epithelial surface by BAL provides opportunities to evaluate and monitor therapeutic strategies directed at reducing the oxidant burden and/or augmenting the antioxidant defense mechanisms in the lower respiratory tract, thereby correcting an oxidant-antioxidant imbalance directly at the site of disease.

Bronchoalveolar Lavage Fluid↗
PubMed1994

[Therapy of lung diseases with anti-oxidants].

Oxidants, highly reactive free radicals, play a major role in the pathogenesis of a variety of inflammatory lung disorders. In the healthy lung, the oxidant burden is balanced by the local antioxidant defenses. However, both an increased oxidant burden and/or decreased antioxidant defenses may reverse the physiological oxidant-antioxidant balance in favour of oxidants, leading to lung injury. This concept points to an obvious therapeutic strategy: augmentation of the antioxidant screen of the lung to prevent oxidant-mediated tissue damage. Studies using reduced glutathione (GSH), the major pulmonary antioxidant, as a model therapeutic agent demonstrate that GSH can be administered directly to the respiratory epithelial surface by aerosol and is fully functional as an antioxidant both in vitro and in vivo. In pulmonary diseases such as idiopathic pulmonary fibrosis or following HIV-infection GSH aerosol therapy not only normalises deficient pre-therapy GSH-levels in the lung, but is capable of favourably influencing cellular events such as oxidant release by pulmonary inflammatory cells. These results suggest that it is possible to use antioxidants to reverse the imbalance between oxidants and antioxidants at the site of oxidant injury to prevent the progressive tissue damage in lung disorders characterised by high oxidant states.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Epidemiology of tuberculosis in patients with HIV infection of the Frankfurt University Clinic].

Frequency and risk of tuberculosis were studied among a large group of HIV-infected patients (n = 2556), 869 of whom had AIDS, over a period of ten years (February 1982 through February 1992) at the University Hospital Frankfurt. A total of 148 (5.8%) out of 2.556 patients had tuberculosis. With increasing immunodeficiency, the frequency of tuberculosis rose. The rate of tuberculosis in post-mortem was even higher, i.e. 17.3%. I.v. drug-addict AIDS patients were inflicted with 18.5% considerably more often than homo-/bisexual patients with 12.3%. The same holds true with 25% of tuberculosis infections for AIDS patients from endemic areas as compared with 13% for patients from countries with lower tuberculosis incidence. 18% of patients contracted tuberculosis already at > 200 CD4-positive cells/microliters before AIDS manifestation. Coming from endemic areas, drug addiction and lower number of T-cells signify a high risk for HIV-infected patients to acquire a post-primary or primary tuberculosis, respectively. HIV-infected patients represent a relevant danger of infection for partners and health-care personnel. In contrast to the United States, no increase in the tuberculosis incidence, except for some areas like Frankfurt, has been noted. Preventive measures, which include the IHN prophylaxis for patients with T-cell counts < 150/microliters, should be discussed.

AIDS-Related Opportunistic Infections↗
PubMed1993

Activation of alveolar macrophages in asymptomatic HIV-infected individuals.

After the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection during the progression of this immune dysfunction, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system, during the asymptomatic phase of HIV infection. Compared to normals, in HIV-infected individuals the class II MHC molecules DR, DQ, and DP were all expressed more frequently and in greater cell surface density on AM (p < 0.03, all comparisons), and there was increased spontaneous release of superoxide anion (O2-.) by AM (p < 0.002). To gain insight into whether the activation of the AM was an inherent property of the cells or dependent on the in vivo milieu, AM were evaluated after 24 h in culture for O2-. release. In contrast to the findings in fresh AM, after 24 h in culture, O2-. release by HIV AM was not different from normals (p > 0.7), suggesting that these AM had been activated in vivo. To assess whether IFN-gamma could be mediating these effects, mRNA levels of the IP-10 gene (a gene specifically induced by increased concentrations of IFN-gamma) were quantified in AM. Strikingly, the IP-10 gene was expressed only in AM of HIV-seropositive individuals, suggesting the AM had been exposed to IFN-gamma in vivo. Overall, these observations are consistent with the concept that the HIV-seropositive state is associated with activation of AM, in part due to local exposure to IFN-gamma.

Adult↗
PubMed1993

Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.

BACKGROUND: Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence. METHODS: Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration. RESULTS: Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed. CONCLUSIONS: It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals.

Adult↗